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Correlations between plasminogen activator inhibitor-1 and peritoneal transport in pediatric CCPD patients
1Department of Pediatrics, State University of New York at Stony Brook, USA.
Insights
Plasminogen activator inhibitor-1 (PAI-1) levels in peritoneal dialysis patients increased during treatment, inversely correlating with ultrafiltration. Peritonitis episodes were linked to higher PAI-1 release, suggesting local production impacts fluid removal.
Area of Science:
- Nephrology
- Physiology
- Biochemistry
Background:
- Plasminogen activator inhibitor-1 (PAI-1) regulates plasminogen activators and extracellular matrix (ECM) accumulation.
- Peritoneal ECM influences peritoneal transport, making PAI-1 a potential factor in water and solute movement.
Purpose of the Study:
- To investigate the relationship between dialysate PAI-1 levels and peritoneal transport during peritoneal equilibration tests (PET).
- To explore the impact of PAI-1 on ultrafiltration and its association with peritonitis in pediatric peritoneal dialysis patients.
Main Methods:
- Examined linear correlations between dialysate PAI-1 and PET variables in six pediatric patients on continuous cycler-assisted peritoneal dialysis.
- Measured PAI-1 levels in dialysate at 0 and 4 hours, alongside ultrafiltration (UF) and albumin saturation indices.
Main Results:
- Dialysate PAI-1 levels significantly increased during the 4-hour dwell time.
- Elevated PAI-1 changes (PAI4-0) negatively correlated with net ultrafiltration (UF).
- Increased PAI-1 production/release was associated with a higher number of peritonitis episodes.
Conclusions:
- Elevated dialysate PAI-1 during PET likely results from local peritoneal production and release.
- PAI-1 levels exhibit an inverse relationship with ultrafiltration volume.
- Repeated peritoneal inflammation correlates with increased PAI-1 production and release into the peritoneum.
Objective:
Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of plasminogen activators and has been shown to be involved in the accumulation of extracellular matrix (ECM) in various tissues. Since peritoneal ECM is a resistance site for peritoneal transport, the production and release of PAI-1 in the peritoneum may affect the peritoneal transport of water and small solutes.
Design:
The linear correlations between the dialysate PAI-1 levels and the variables of peritoneal transport during peritoneal equilibration tests (PET) were examined.
Setting:
A tertiary university hospital.
Patients:
Six stable pediatric patients (age 10.8 +/- 4 years) undergoing continuous cycler-assisted peritoneal dialysis were included.
Interventions:
None.
Results:
All data are mean +/- SD. There was a positive correlation between the infused volume and the net ultrafiltration (UF, 198 +/- 127 mL, r = 0.82, p < 0.05). The dialysate PAI-1 levels increased during the dwell time (2.44 +/- 2.23 ng/mL or 2.46 +/- 1.72 micrograms at 4 hours vs 0.04 +/- 0.1 ng/mL or 0.04 +/- 0.09 micrograms at 0 hour, p < 0.05). The saturation indices (dialysate/plasma ratio) of PAI-1 and albumin at 4 hours were 1.05 +/- 1.21 and 0.028 +/- 0.004, respectively. The changes from 0 hour dwell to 4 hour dwell in the dialysate PAI-1 concentration (PAI4-0, 2.4 +/- 2.2 ng/mL) or amount corrected to body surface area (APAI4-0/BSA, 2.61 +/- 2.11 micrograms/m2) negatively correlated with UF or UF/body surface area and positively correlated with the number of episodes of peritonitis. There was no correlation between PAI4-0,APAI4-0/BSA, or plasma PAI-1 concentration and the mass transfer coefficient and clearance of either urea or creatinine.
Conclusions:
The elevated PAI-1 level during the PET was likely from the local production and release of PAI-1. It had an inverse relationship with the amount of ultrafiltration. Repeated inflammation of the peritoneum was associated with an increased production and release of PAI-1 into the peritoneum.